Comparative genomics of carbapenemase-producing <i>Morganella spp</i>
Notice bibliographique
Résumé
ABSTRACT Background Morganella are opportunistic pathogens involved in various infections. In Morganella , intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium. Methods From 2013 to 2021, 172 highly drug-resistant (XDR) Morganella isolates from 8 European countries and Canada, two reference strains from the Pasteur Institute collection and two susceptible isolates were characterized by WGS, antimicrobial susceptibility testing and biochemical tests. Complete genomes from Genbank (n=103) were included for genomic analysis. Intrinsic resistance mechanism to polymyxins was deciphered by combining genetic analysis with mass spectrometry on the lipid A. Findings Morganella could be separated into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii included two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius . Intrinsic resistance to tetracycline and conservation of metabolic pathways correlated this refined taxonomy. CP were mostly identified among five ‘high-risk’ clones of M. morganii subsp. morganii . A single nucleotide polymorphism (SNP) cut-off of 100 was used to decipher outbreaks involving this species. Cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards the 172 XDR Morganella spp. isolates of our collection (including 145 CP) except for metallo-β-lactamase-producers. The intrinsic resistance to polymyxins corresponds to the addition of L-Ara4N on the lipid A. Interpretation This global characterization of the widest collection of XDR Morganella spp. highlighted the need to clarify the taxonomy, deciphered intrinsic resistance mechanisms and paved the way for further genomic comparisons. Funding None RESEARCH IN CONTEXT Evidence before this study On January 28 th 2022, we have searched for the terms “ Morganella ” and “carbapenemase” in all published reports available in PubMed with no language restriction. We identified a total of 43 articles and most of them (41/43) corresponded to a report of a single isolate of carbapenemase-producing Morganella morganii . Only one article aimed to decipher the antimicrobial susceptibility on a collection of Proteus, Providencia and Morganella isolated from global hospitalized patients with intra-abdominal and urinary tract infections. However, this collection only included 7 M. morganii isolates. On March 2021, when we finished the inclusions in our collection, only 104 genomes of Morganella spp. were available in the NCBI database. Since September 2021, very few reports were published on carbapenemase-producing Morganella with the exception of a study from Xiang G et al . reported 40 multi-drug resistant M. morganii isolates recovered from three hospitals in China from 2014 to 2020. Unfortunately, this collection included only two carbapenemase-producing M. morganii isolates (one OXA-48 and one IMP-1). A report of KPC-producing M. morganii in Japan and a longitudinal study of carbapemase-producing Enterobactrales in Taiwan that did not focused on Morganella. We also searched in PubMed for the terms ‘ Morganella sibonii ” or “ Morganella psychrotolerans ” in all published reports with no language restrictions. Our search identified a total of 20 articles. None of them was related to antimicrobial resistance and no study deciphered the Morganella spp. epidemiology on clinical isolates. Added values of this study This global characterization involved the widest collection of Morganella spp. isolates ever reported (barely doubling the number of Morganella spp. genomes in Genbank). In addition, 145 isolates of this worldwide collection made of 172 multidrug resistant Morganella spp. were carbapenemase producers for which therapeutic alternatives are scarce due to intrinsic resistance to last resort molecules, such as polymyxin. First, we found that cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards XDR Morganella spp. isolates except for metallo-β-lactamase-producers. Then, we observed that carbapenemase-encoding genes were present in different Morganella species highlighting necessary changes in the taxonomy. Morganella genus could be divided into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii includes two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius . We demonstrated that this refined taxonomy correlated with the intrinsic resistance to tetracycline, which was found only in M. sibonii , as well as several metabolic pathways ( e . g . trehalose assimilation, type III (T3SS) and type IV secretion system (T6SS), etc.…). In addition, we highlighted five “high-risk” clones of carbapenemase-producing M. morganii subsp. morganii that have already disseminated worldwide. Combining whole genome sequencing (WGS) data with epidemiological investigations, we demonstrated that a cut-off of 100 single nucleotide polymorphisms (SNPs) could be used to discriminate clonally-related from sporadic independ
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».